The goal of this project is to characterize the function of B lymphocyte Fc-gamma receptors. Previous findings indicate that the Fc-gamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens, c) LYM antigens, d) surface IgM, and e) surface IgD. Each of these interactions is distinct, specific, and non-random. Studies utilizing antigen-antibody complexes indicate that B lymphocyte Fc-gamma receptors cross-linked by their physiologic ligand downregulate B lymphocyte differentiation without affecting proliferation. Resting but not activated B lymphocytes are susceptible to this negative regulation. Occupancy of B lymphocytes surface IgK by a separate ligand is necessary for inhibition to occur, suggesting that the previously described interaction between these two membrane receptors may be involved in generating the negative signal. Studies using monoclonal anti-Fc-gamma antibody (2.4G2) in a variety of forms including native, chemically cross-linked into homodimers or heterodimers with anti-delta or F(ab')2 anti-mu antibodies, and on a Sepharose matrix indicate that the monoclonal antibody only generates the negative regulatory signal if effective cross-linking of the receptor is obtained. IL-4 specifically induces a marked (90%) loss of binding of complexes to B lymphocyte Fc-gamma-R II. The IL-4 induced loss of binding of complexes was time and temperature dependent and was reversible. IFN- gamma could partially prevent this effect. The loss-of binding of complexes did not appear to be due simply to a loss of expression of FC-gamma-R II because IL-4 induced only a specific monoclonal antibodies. Stimulation of or with a combination of PMA and CA(2+) ionophore of complexes, suggesting that loss of Fc-gamma-R II via 2 pathways. Inhibition of protein synthesis loss of complex binding, suggesting that this FC-gamma-R II with another membrane molecule.